Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants

Abstract

Rationale: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.

Objective: To assess changes in pulmonary function during the first year of life in CF NBS infants.

Methods: Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV₀.₅) were measured at 3 months and 1 year of age.

Main results: Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV₀.₅ improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV₀.₅ was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV₀.₅ at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year.

Conclusions: This is the first study reporting improvements in FEV₀.₅ over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.

Keywords: Cystic Fibrosis; Lung Physiology; Paediatric Lung Disaese.

Figure 1

Success rates for recruitment and achievement of technically acceptable infant pulmonary function data. NBS, newborn screened; PFTs, pulmonary function tests; LCI, lung clearance index; FRC, functional residual capacity; MBW, multiple breath inert gas washout; pleth, plethysmographic technique; RVRTC,Raised Volume Rapid Thoraco-abdominal Compression, from which forced expired flows and volumes were derived. See online supplementary table E1 for details of PFT success on each test occasion.

Figure 2

Relationship between pulmonary function at 3 months and 1 year in newborn screened CF infants. The 95% limits of ‘normal range’ (97.5th centile for Lung Clearance Index (LCI) and functional residual capacity (FRC) and 2.5th centile for FEV_0.5) are represented by vertical dashed lines at 3 months (3m) and horizontal lines at 1 year (1yr). Those with normal pulmonary function tests on both occasions fall within the lower left quadrant for LCI and FRC, and upper right quadrant for FEV_0.5. Infants with abnormal LCI at 3 months but normal LCI at a year, lie within the lower right quadrant (A), while those with abnormal FEV_0.5 at 3 months which has normalised by 1 year are within the left upper quadrant of (C).

Figure 3

Comparison of current lung function results in infants with cystic fibrosis (CF) and healthy controls (C) at ∼1 year of age, with previously published results. Data expressed as mean (95% CI). To allow direct comparison with previously published studies, Lung Clearance Index is presented in absolute units, whereas FEV_0.5 is expressed as z-scores, based on different reference equations according to each author. The dashed horizontal line at 0 z-scores equates to 100% predicted based on a healthy population. Control data were not available in all studies. NBS, newborn screening.